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   2008| March-April  | Volume 40 | Issue 2  
    Online since June 4, 2008

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A review on plant-derived natural products and their analogs with anti-tumor activity
KK Dholwani, AK Saluja, AR Gupta, DR Shah
March-April 2008, 40(2):49-58
DOI:10.4103/0253-7613.41038  PMID:21279166
Traditional medicines, including Chinese herbal formulations, can serve as the source of potential new drugs, and initial research focuses on the isolation of bioactive lead compound(s). The development of novel plant-derived natural products and their analogs for anticancer activity details efforts to synthesize new derivatives based on bioactivity- and mechanism of action-directed isolation and characterization coupled with rational drug design - based modification. Also, the anticancer activity of certain natural products and their analogs can be enhanced by synthesizing new derivatives based on active pharmacophore models; drug resistance and solubility and metabolic limitations can be overcome by appropriate molecular modifications; and new biological properties or mechanisms of action can be added by combining other functional groups or molecules. Preclinical screening for in vitro human cell line panels and selected in vivo xenograft testing then identifies the most promising drug development targets.
  41 15,947 1,873
Paralytic effect of alcoholic extract of Allium sativum and Piper longum on liver amphistome, Gigantocotyle explanatum
TU Singh, D Kumar, SK Tandan
March-April 2008, 40(2):64-68
DOI:10.4103/0253-7613.41040  PMID:21279168
Objective: To investigate the effects of alcoholic extract of Allium sativum and Piper longum on the muscular activity of a parasitic amphistome, Gigantocotyle explanatum. Materials and Methods: Amphistomes were isometrically mounted to record the spontaneous muscular activity by using Chart 4 software program (Power Lab, AD Instruments, Australia) and to examine the effects of cumulative doses (100, 300, 1000, and 3000 µg/ml) of the plant extracts on the amplitude (g), frequency (per 10 min), and baseline tension (g) of the spontaneous muscular activity of the amphistome. Results: Alcoholic extract of A. sativum produced significant reduction in the frequency and amplitude of contractile activity of the amphistome at 1000 and 3000 µg/ml bath concentrations. Complete paralysis of the amphistome was observed after 15 min of addition of 3000 µg/ml concentration. Alcoholic extract of P. longum also caused paralysis following 15-20 min exposure of the amphistome to 3000 µg/ml concentration. In both the cases the amphistomes did not recover from paralysis following 2-3 washes. Conclusion: The observations demonstrate the paralytic effect of alcoholic extract of A. sativum and P. longum on G. explanatum.
  12 9,399 525
Effects of low-level lead exposure on blood pressure and function of the rat isolated heart
Badalzadeh Reza, Norouzzadeh Ali, Heydari Azhdar, Asgari Alireza, Khoshbaten Ali
March-April 2008, 40(2):69-72
DOI:10.4103/0253-7613.41041  PMID:21279169
Objective: Exposure to low levels of lead acetate can induce hypertension in both humans and experimental animals. The exact mechanisms of lead-induced hypertension are not well understood, but its pathogenesis could be explained by the changes in heart rate and contractility. Materials and Methods: In the present study, the effects of exposure to 100 ppm of lead in drinking water (for periods of 4, 8, and 12 weeks) on blood pressure and some physiologic parameters (eg, electrocardiography [ECG], heart rate [HR], cardiac contractility, and coronary flow) of isolated beating rat heart was investigated using the Langendorff isolated heart apparatus. The isolated hearts were perfused with Krebs-Henseleit solution (37°C; pH 7.4; gassed with 95% O 2 + 5% CO 2 ). All data were digitized by a software program for further analysis. Results: The blood pressure in the 8- and 12-week lead-exposed groups was significantly increased as compared to the control group. The ECG showed arrhythmias and conduction abnormalities only in the late phases of exposure (12 weeks). The HR and contractility were significantly higher in the 8- and 12-week lead-treated rats but not in the 4-week group. No significant changes were observed in coronary flow. Conclusion: These results indicate that: 1) low levels of lead exposure do not significantly affect the ECG in the early phase, 2) low levels of lead exposure causes ECG changes in the late phases of exposure, and 3) this level of lead exposure can increase HR and cardiac contractility but has no effect on coronary flow.
  7 9,286 333
Isoniazid causing pleural effusion
SK Singh, Z Ahmad, DK Pandey, V Gupta, S Naaz
March-April 2008, 40(2):87-88
DOI:10.4103/0253-7613.41045  PMID:21279173
Isoniazid (INH) is a first-line antitubercular drug. We report a case of a patient who developed a pleural effusion 2 months after starting antitubercular treatment for spinal tuberculosis. Isoniazid was found to be the culprit and its discontinuation caused subsidence of the effusion.
  5 5,159 290
Mechanisms responsible for the vascular effect of aqueous Trigonella foenum-graecum leaf extract in diabetic rats
Mohammad Reza Vaez Mahdavi, Mehrdad Roghani, Tourandokht Baluchnejadmojarad
March-April 2008, 40(2):59-63
DOI:10.4103/0253-7613.41039  PMID:21279167
Background and Objective: Since a beneficial vascular effect of aqueous leaf extract of Trigonella foenum-graecum (TFG) has previously been reported, this study was conducted to evaluate the underlying mechanisms, including the role of nitric oxide (NO) and cyclooxygenase pathways, in diabetic rats. Materials and Methods: Male Wistar rats were divided into control, extract-treated control, diabetic, and extract-treated diabetic groups. Diabetes was induced by a single i.p. injection of streptozotocin (STZ; 60 mg/kg). Treatment groups received TFG extract (200 mg/kg; ip.) every other day for 1 month. Contractile reactivity of the thoracic aorta to KCl and noradrenaline (NA) and relaxation response to acetylcholine (ACh) were determined. For determination of the participation of NO and prostaglandins in the relaxation response to ACh, aortic rings were incubated for 30 min before the experiment with N-nitro-l-arginine methyl ester (L-NAME) and/or indomethacin (INDO). Results: The diabetic state significantly increased the maximum contractile response to KCl and NA (P < 0.01-0.005) and reduced the maximum relaxation due to ACh (P < 0.01) as compared to controls and treatment with TFG extract in the diabetic group significantly improved these changes relative to the untreated diabetic group (P < 0.05). With L-NAME pretreatment, no significant difference between diabetic and extract-treated diabetic groups was found out. On the other hand, there was a significant difference between these two groups following INDO pretreatment (P < 0.05). Conclusion: Intraperitoneal administration of aqueous leaf extract of TFG for one month could improve some functional indices of the vascular system in the diabetic state and endothelium-derived prostaglandins are essential in this respect.
  3 6,122 636
Demonstration of LanthaScreen™ TR-FRET-based nuclear receptor coactivator recruitment assay using PHERAstar, a multi-detection HTS microplate reader
Prashanth C.G D'Souza, Nafisa Ally, Amit Agarwal, Padmaja Rani, Meenakshi Das, Dolly Sarma
March-April 2008, 40(2):89-90
DOI:10.4103/0253-7613.41046  PMID:21279174
An attempt was made to demonstrate the possibility of performing LanthaScreen™ TR-FRET based nuclear receptor coactivator recruitment assay using PHERAstar, a multi-detection HTS microplate reader. LanthaScreen™ nuclear receptor coactivator recruitment assay (M/s Invitrogen corporation, USA) was performed using PPAR-gamma receptor preparation in the agonist mode. TR-FRET measurements were done on PHERAstar, a multimode microplate reader (BMG LABTECH, Germany). The Lanthascreen PPAR gamma coactivator recruitment assay was successfully performed in the PHERAstar, multimode microplate reader. This was evidenced by an assay robustness score (Z') of 0.71. The current work demonstrates the suitability of using PHERAstar, a multi-detection HTS microplate reader.for performing LanthaScreen™ TR-FRET based nuclear receptor coactivator recruitment assays.
  2 4,511 182
Registration of clinical trials: An idea whose time has come!
Arun Bhatt
March-April 2008, 40(2):47-48
DOI:10.4103/0253-7613.41037  PMID:21279165
  2 3,994 689
Is the combination of enalapril and losartan irrational?
DM Parmar, SP Jadav
March-April 2008, 40(2):91-91
DOI:10.4103/0253-7613.41047  PMID:21279175
  1 4,308 379
Protective effect of palm vitamin E and α-tocopherol against gastric lesions induced by water immersion restraint stress in Sprague-Dawley rats
Ibrahim Abdel Aziz Ibrahim, Kamisah Yusof, Nafeeza Mohd Ismail, Nur Azlina Mohd Fahami
March-April 2008, 40(2):73-77
DOI:10.4103/0253-7613.41042  PMID:21279170
Objective: Stress can lead to various changes in the gastrointestinal tract of rats. The present study was designed to compare the effect of palm vitamin E (PVE) and a-tocopherol (a-TF) supplementations on the gastric parameters important in maintaining gastric mucosal integrity in rats exposed to water immersion restraint stress (WRS). These parameters include gastric acidity, plasma gastrin level, gastric prostaglandin E 2 (PGE 2 ), and gastric lesions. Materials and Methods: Sixty male Sprague-Dawley rats (200-250 g) were divided into three equal groups: a control group, which received a normal rat diet (RC), and two treatment groups, receiving oral supplementation of either PVE or α-TF at 60 mg/kg body weight for 28 days. Each group was further divided into two groups: the nonstress and stress groups. The stress groups were subjected to 3.5 h of WRS once at the end of the treatment period. Blood samples were then taken to measure the gastrin level, after which the rats were killed. Gastric juice was collected for measurement of gastric acidity and gastric tissue was taken for measurement of gastric mucosal lesions and PGE 2 . Results: Exposure to stress resulted in the production of gastric lesions. PVE and a-TF lowered the lesion indices as compared to the stress control group. Stress reduced gastric acidity but pretreatment with PVE and α-TF prevented this reduction. The gastrin levels in the stress group were lower as compared to that in the nonstress control. However, following treatment with PVE and α-TF, gastrin levels increased and approached the normal level. There was also a significant reduction in the gastric PGE 2 content with stress exposure, but this reduction was blocked with treatment with both PVE and α-TF. Conclusion: In conclusion, WRS leads to a reduction in the gastric acidity, gastrin level, and gastric PGE 2 level and there is increased formation of gastric lesions. Supplementation with either PVE or α-TF reduces the formation of gastric lesions, possibly by blocking the changes in the gastric acidity, gastrin, and gastric PGE 2 induced by stress. No significant difference between PVE and α-TF was observed.
  1 6,535 361
Economic impact of interventional study on rational use of antiseptics and disinfectants in Super Speciality Hospital of Nagpur
Vandana Agarwal, Kunda Gharpure, Vijay Thawani, Sushil Makhija, Anita Thakur, Rajaram Powar
March-April 2008, 40(2):78-83
DOI:10.4103/0253-7613.41043  PMID:21279171
Objective: To measure the impact of interventions on rational use of antiseptics and disinfectants (A and D) for cost containment in Super Speciality Hospital (SSH) of Government Medical College, Nagpur (GMCN), India. Materials and Methods: This study was conducted from October 2003 to March 2007 in SSH of GMCN. In the pre-interventional phase (Phase-I), purchase, stocking and distribution of A and D was studied to find problem areas. Based on this formative data an intervention was planned (Phase-II) during which rationing of the A and D was done. Rational quantities needed for different A and D procedures were calculated based on recommendations of National Aids Control Organization (NACO) with modifications to suit our hospital setup. Detailed information, education, communication and training about rational use of A and D were provided to the hospital staff. In the post-interventional phase (Phase-III), the use of A and D was rationalized at the distribution level and the efficacy of in-use A and D was tested at user sites. Data about medicine expenditure, patient record and A and D usage in various departments was obtained from hospital records. Savings on A and D as against total annual medicine expenditure was calculated taking the cost of A and D in the post-intervention period. Results: The expenditure on A and D as a result of intervention decreased by 20.7%. Out of the total medicine expenditure, the expenditure on A and D which accounted for 6.2% before intervention, decreased to 1.95% after the intervention. Conclusion: The information, education and communication (IEC) interventions attempted by us resulted in significant decrease in the use and expenditure of A and D.
  1 5,299 274
Effect of erythromycin and rifampicin on monoethylglycinexylidide test
Satish Balkrishna Bhise, Remeth Jacky Dias
March-April 2008, 40(2):84-86
DOI:10.4103/0253-7613.41044  PMID:21279172
Background: The dynamic liver function test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX) provides a direct measure of the actual functional state of the liver. Cytochrome P450 (CYP) 3A4 has been proposed as the main CYP isoform responsible for MEGX formation. The concomitant use of either CYP3A4 inducer rifampicin or CYP3A4 inhibitor erythromycin may influence the results of MEGX test. Hence, the objective of this study was to evaluate the effect of a CYP3A4 inhibitor erythromycin and inducer rifampicin on the MEGX test. Materials and Methods: The study included 20 healthy male volunteers whose routine laboratory tests were normal. As per study protocol, MEGX test was carried out in all the participants after an overnight fast. All the participants were given 1 mg/kg lidocaine dose intravenously and MEGX concentration at 30 and 60 min after IV dose was measured using HPLC. These MEGX values served as control values. Ten subjects received 600 mg/day erythromycin orally for six days while remaining ten participants received 600 mg/day rifampicin orally for six days. On the sixth day, MEGX test was carried out two hours after the last dose. Result: Rifampicin increased the mean plasma concentration of MEGX 30 from 93.94 ± 26.31 to 98.54 ± 24.94 µg/ml (P = 0.085) and MEGX 60 from 134.34 ± 35.42 to 136.36 ± 33.14 µg/ml (P = 0.051). Erythromycin lowered the serum concentration of MEGX 30 from 101.37 ± 39.39 to 96.67 ± 36.09 µg/ml (P = 0.128) and MEGX 60 from 142.52 ± 42.65 to 138.98 ± 40.23 µg/ml (P = 0.159). Conclusion: It can be concluded from this study that the MEGX test is not affected by concomitant administration of CYP3A4 modifiers rifampicin and erythromycin.
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